A reliable, quantitative method for the measurement of molecular changes associated with early cataractogenesis has long been an important goal of human clinical cataract research. Such a method would allow researchers and physicians to (a) assess the effectiveness of anticataract drugs; (b) determine the effects of pharmacological agents or radiation used in the treatment of systemic diseases on the formation of cataracts; and (c) provide a quantitative basis for the medical decision to intervene surgically or pharmaceutically in the treatment of cataract.
In recent years quasi-elastic light scattering (QLS) has been used to study the ocular lens in vivo and in vitro. A method and apparatus for analyzing QLS is described in U.S. Pat. Nos. 4,957,113, and 5,072,731, respectively, which are incorporated herein by reference.
The techniques described in the above-referenced patents are capable of quantitatively measuring the amount of light scattered by diffusing chemical species in a medium, as well as their rates of diffusion. With QLS, the time fluctuations in intensity of light scattered by a selected small volume in the lens which is illuminated by an incident laser beam are studied. The scattered light intensity fluctuates in time because of the Brownian motion of the scattering elements. Brownian motion is defined as the motion of macromolecules caused by thermal agitation and the random striking by neighboring molecules in a solution. In the lens of the human eye, the Brownian motion of protein molecules may be recorded and analyzed by quasi-elastic light scattering.
Research has shown that the principal scattering elements within the lens are the molecular constituents of the fiber cells. These constituents are principally globular proteins called crystallins. The aggregation of small proteins within the lens is the very first stage in the process of cataractogenesis. As the light scattering becomes more pronounced, it becomes noticeable to the clinician and is termed a cataract. However, this represents a late stage of a continuous process of increase in light scattering with time within the lens. By using information obtained from the light scattered by the various fast and slow moving protein species, it is possible to determine the degree of aggregation and thus the degree of cataractogenesis before it would be noted clinically.
The intensity fluctuations of the scattered light are detected by collecting the light scattered from the illuminated volume in the eye lens and focusing this light onto the surface of an optical detector such as a photomultiplier tube or solid-state photodiode. The output of the detector is a photoelectric current whose temporal fluctuations are synchronized with the fluctuations in the scattered light intensity. The temporal fluctuations in the photoelectric current can be mathematically analyzed to provide a quantitative measure of the degree of cataractogenesis.
The experimental data is typically expressed in the form of the temporal autocorrelation function, C(.tau.), of the intensity of the detected scattered light from the scattering medium as a function of the delay time, .tau.. From the mathematical form of the autocorrelation function, it is possible to determine the diffusivity of the scattering elements undergoing Brownian movement. The collected data is fit to a model autocorrelation function. The fitted parameters of the model autocorrelation function have been shown clinically to provide an accurate quantitative measure of the source of increased light scattering on a molecular level long before cataract formation could be detected visually by either the subject or the physician.
The QLS inventions described in the above-referenced patents have provided tools to detect cataract formation at a very early stage. However, the research instruments of the prior art are not always efficient from the clinical perspective. A practical clinical instrument must perform the QLS measurements quickly and accurately. Data must be collected quickly to minimize patient discomfort and to minimize effects of artifact such as patient eye movement. For this reason, a small number of data points collected over a relatively brief period of time must provide the desired information. The curve fitting routine must accurately fit the model autocorrelation function and provide the physician with reliable results from which to make a diagnosis. If there are too few parameters in the model autocorrelation function, then certain characteristics in the data will not be analyzed. If there are too many parameters in the model autocorrelation function, then the parameters will be statistically interdependent and may have diminished meaning when interpreting data. Therefore, it can be appreciated that there is a significant need for a method and apparatus for detecting cataractogenesis that is applicable to clinical situations. The present invention fulfills this need and provides other related advantages.